电离辐射通过转化生长因子-β-介导的上皮-间质转换来倡导癌细胞的侵袭迁移

Int J Radiat Oncol Biol Phys 2011 Dec;81 (5): 1530-7. [IF:4.503]Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-Beta-mediated epithelial-mesenchymal transition.Zhou YC , Liu JY , Li J , Zhang J , Xu YQ , Zhang HW , Qiu LB , Ding GR , Su XM , Mei-Shi , Guo GZ .Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi'an, China; Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an, China.第四军医大学西京医院放射科

AbstractTo examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-β)-mediated epithelial-mesenchymal transition (EMT). Six cancer cell lines originating from different human organs were irradiated by (60)Co γ-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-β in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-β signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. After irradiation with γ-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-β were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-β signaling. These results suggest that EMT mediated by TGF-β plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

摘要 ：深入探讨紫外光否可通过转化生长因子-β（TGF-β）-抑制的黏膜-黏膜细胞切换 (EMT)来推动癌细胞的侵袭迁入。使用年均2Gy(60)Coγ线照射源自生命器官的6种癌细胞，记录与EMT特别的推移，这包括分别利用显微技术，酵素印迹方通则，免疫荧光技术，刷试验中和Transwell小室试验中来观察并扫描细胞组织形态，EMT标识，侵袭迁入灵活性等。运用于酶联免疫吸附通则扫描这些癌细胞里面TGF-β蛋白水平，利用特别抑制剂SB431542来评估TGF-β频率通路在紫外光EMT里面的作用。经过年均为2Gy照射的癌细胞里面存在间叶细胞的表达，与实为照射组比起其黏膜标识减少，间叶细胞标识增加，同时其侵袭移转到灵活性提高，TGF-β蛋白水平也进一步提高。进一步发现由A549紫外光诱导的EMT可通过对TGF-β频率抑制发生反转。这些得出结论TGF-β抑制的EMT在紫外光诱导提高癌细胞侵袭移转到灵活性里面起着关键作用。

撰稿人： lizexiu